Recent work in animal models of carcinogenesis have demonstrated that ornithine decarboxylase (Odc) is a susceptibility gene for skin cancer. The expression of this gene is known to be regulated by an enormous variety of environmental stimuli, including, but not limited to, chemical carcinogens, tumor promoters, toxins and UV irradiation. A proximal regulator of Odc expression is Myc, the product of the c-myc gene. In humans, there are 2 allelic variants of the Odc gene defined by a single nucleotide change in a region of the gene responsible for regulation by Myc. The work proposed in this application will first determine whether the 2 allelic variants are functionally different with respect to transactivation by Myc and will also test the hypothesis that the minor Odc allelelic variant confers increased risk for environmentally-induced squamous cell carcinoma. The results of our work could identify one of the environmentally-responsive genes which determine, in concert with other genes, an individual's susceptibility to skin cancer.